The UK Department of Health proposed a dimensional model for dual diagnosis, represented by two axes, one horizontal expressing the severity of the non-addiction mental disease and a vertical one which represents the severity of the psychoactive substance abuse disorder⁽⁴⁾.

Schizophrenia and psychoactive substance use disorders

DSM-5 recommends that psychotic symptoms should not be attributed to the consumption of a psychoactive substance, and that these symptoms should persist for more than one month after the discontinuation or abstinence from the respective substance⁽²⁾.

ICD-10 mentions that psychotic symptoms induced by the misuse of a psychoactive substance can persist for up to six months, but the diagnosis of schizophrenia can be made after one month of abstinence from the addictive substance if the symptomatology remains florid⁽⁸⁾.

From a neurobiological perspective, functional neuroimaging research has highlighted the involvement of common brain circuits and regions that overlap between both substance use disorders and major non-addiction mental disorders (Figures 8 and 9). It can be noted that regions such as the orbital prefrontal cortex, ventromedial prefrontal cortex, dorsolateral prefrontal cortex, nucleus accumbens, amygdala and ventral tegmental area are regions that are often implicated in the pathogenesis of disorders that constitute dual diagnosis. Additionally, complex neural circuits and networks connecting these regions are dysfunctional, involving the reward network and mesolimbic pathway, which are hyperactive, while the top-down inputs regulating social behavior or emotion-based behavior are inefficient and exhibit hypoactivity. Finally, the dorsolateral prefrontal cortex, which plays an essential role in cognitive processes such as decision-making, problem-solving, working memory and speed of information processing, leads to severe impairment in the overall behavior and global functionality of the affected individual⁽⁹⁾.
 

Schizophrenia and nicotine addiction

Regarding smoking, some literature data suggest that the alpha-7 nicotinic receptor may play a role, as its stimulation could improve cognitive symptoms that are intrinsic to the disease⁽¹⁰⁾.

Inversely, other studies have evidenced that nicotine has a selectively increased affinity for the α4β2 nicotinic receptors, which would exacerbate dopaminergic dysfunction at the mesolimbic level, and maternal exposure to it during pregnancy would increase the risk of schizophrenia in the offspring due to neurodevelopmental impairment^(11,12).  A negative therapeutic consequence is that smoking affects the metabolism of antipsychotics that are substrates for the CYP1A2 cytochrome, such as clozapine and olanzapine, thereby leading to a significant decrease in their plasma concentrations⁽¹³⁾.
 

Dual diagnosis prevalence

The increased co-occurrence between alcohol use disorders and schizophrenia can be partially determined by a common genetic vulnerability, such as the polymorphism of the gene that encodes the synthesis of brain-derived neurotrophic factor (BDNF), which is also confirmed by genome-wide association studies^(15,16).
 

Schizophrenia and cannabis use disorder

Cohort studies have revealed that the frequency and cumulative amount of cannabis use have exponentially correlated with the likelihood of subsequently developing schizophrenia and are correlated with a younger age⁽¹⁷⁾.

An impressive meta-analysis that examined data from several studies found an odds ratio of 3.90 (95% CI; 2.84-5.34) for the risk of schizophrenia and other psychoses among heavy cannabis users compared to non-users, with a dose-dependent effect⁽¹⁸⁾.

There are also studies on population cohorts that do not confirm cannabis use as a risk factor for the development of schizophrenia, but rather its role as a trigger for the disease in already vulnerable people⁽¹⁹⁾.

Cannabis influences all brain neurotransmissions retrogradely, thereby undermining brain neural dysfunctionality towards psychosis.

Bipolar disorder and psychoactive substance use disorders

Genetic bases

• A study based on a representative cohort of bipolar patients identified the significant association of the protein kinase C iota gene (PRKCI) with the presence of this type of dual diagnosis⁽²⁰⁾.
• Genes involved in the functioning of the HHS axis were identified as significantly associated in patients with bipolar disorder and a disorder induced by the use of psychoactive substances⁽²⁰⁾.

 

Neuroimaging correlations

• Patients with bipolar disorder comorbid with alcohol-induced disorders showed lower concentrations of glutamate in the dorsolateral prefrontal cortex compared to patients who had only bipolar disorder⁽²¹⁾.
• It was revealed a lower gray matter volume in the medial portion of the orbitofrontal cortex compared to their counterparts⁽²²⁾.

Dual diagnosis prevalence

A large meta-analysis, which included data on 218,397 bipolar patients, revealed that the severity of mood pathology directly influenced the association between bipolar disorder and illicit psychoactive substance use. Of the clinical features that were associated with significant drug use, the rapid-cycling subtype of bipolar affective disorder stood out⁽²³⁾.

 

Unipolar depression and psychoactive substance use disorder

Genetic basis

• Genes encode the synthesis of some components mainly involved in synthesizing serotonin, whose activity is reduced in both mental disorders⁽²⁴⁾.
• The frequent coexistence of depression, alcoholism, impulsivity, aggression and suicide could involve the gene that synthesizes the serotonin transporter, SLC6A4⁽²⁵⁾.

 

Arguments based on clinical evidence:

• both depression and addiction to psychoactive substances respond positively to the administration of SSRIs⁽²⁵⁾.

Dual diagnosis prevalence

Taking into account the prevalence of the two nosological psychiatric entities, the comorbidity of depression with addiction to psychoactive substances is the most common.

Establishing the temporal sequence of the appearance of the two mental health problems has more theoretical than practical importance, because the therapeutic approach is highly complex and challenging in both situations.

 

Personality disorders and the use of psychoactive substances

Genetic basis

• In part, there appears to be a common genetic basis for borderline personality disorder (BPD) and substance use disorders (SUDs)⁽²⁸⁾.
• Individual differences between BPD and antisocial personality disorder (ASPD) characteristics have emerged as phenotypic and genetic correlates of lifetime harmful cannabis use⁽²⁹⁾.
• The common etiological model postulates that SUD and PD share an overlapping vulnerability resulting from common etiological factors, such as impulsivity/disinhibition traits⁽²⁹⁾.

 

Clinical and endophenotypic bases

• It seems that the coexistence of personality disorders in cluster C of the DSM (avoidant, obsessive-compulsive, and dependent personality disorder) has been highlighted as participating, as frequently, in the constitution of this type of dual diagnosis. People with personality disorders belonging to the C cluster confronting stressful life events often use psychoactive substances as a dysfunctional coping style⁽²⁸⁾.

 

Neurobiological bases

• Positive Emotionality/Extraversion (EP/E) dimension correlates directly with the number of striatal dopaminergic D2 receptors in the central dopaminergic and reward system⁽³⁰⁾.
• Negative Emotionality/Neuroticism (EN/N) is a second dimension of personality that could be involved in the pathogenesis of addictions, correlated with reduced automatic control of the expression of negative emotions due to the decrease of rACC/vmPFC control over amygdala function⁽³⁰⁾.

Post-traumatic stress disorder and psychoactive substance use disorders

• Difficulties in processing emotions have been identified as underlying in the association of post-traumatic stress disorder with substance use disorders.
• Hypothalamic-pituitary-suprarenal axis dysfunction, with an increase in corticotropin-releasing hormone⁽³²⁾.
• Dysfunctions of the catecholaminergic and serotoninergic systems⁽³²⁾.

Somatoform disorders and the use of psychoactive substances disorders

Among the defining clinical characteristics of somatoform disorders, the presence of somatic or bodily complaints can be noted, along with distorted interpretations of normal bodily sensations with excessive access to help-seeking behaviors.

To the same extent, there is the denial of the psychological causality of the symptomatology and the resorting to self-medication-type behaviors.

Among these behaviors, the consumption of medicinal substances, but also that of psychoactive substances, are frequently the mark of these types of mental disorders^(33,34).

Sixty-eight percent of subjects with lifetime substance use disorders (SUD) reported that body dysmorphic disorder (BDD) contributed to their SUD, and those with both BDD and lifetime SUD had a significantly higher rate of suicide attempts compared to those with BDD alone (p=0.004)⁽³⁵⁾.
 

Adjustment disorders and the use of psychoactive substances

Adjustment disorders are a category of mental disorders frequently encountered in young people in which the inefficiency and maladaptive coping mechanisms favor the triggering of symptoms in the context of psychosocial stressors^(35,36).

These patients refer to addiction-type behaviors as dysfunctional coping patterns, which may precede suicide attempts or self-mutilation behaviors^(35,36).

Studies on adjustment disorders are significantly scarce, their diagnosis being currently discouraged, possibly for certain reasons other than psychiatric or psychopathological ones^(35,36).

Attention deficit hyperkinetic disorder and the use of psychoactive substances

Consumption of psychoactive substances, especially in the sphere of stimulants, has been observed, and it is frequently encountered in the clinical context of dual diagnosis from an early age^(37,38). According to an extensive study carried out in Europe (The International Collaboration on ADHD and Substance Abuse [ICASA]):

• The prevalence of ADHD in adults in treatment for a substance use disorder ranged from 7.6% (95% CI; 4.1-11.1) in the Hungarian sample to 32.6% (95% CI; 26.4-38.8) in the Norwegian sample⁽³⁷⁾.
• Furthermore, higher prevalence rates were observed for illicit drug dependence compared to alcohol dependence and a higher prevalence in outpatient services compared to hospital settings^(38,39).

Intervention strategies – principles and requirements

• The development of integrated care services, which interconnect services dedicated to addiction problems with those dedicated to mental health.
• Their adaptation to local needs.
• The individualization of the therapeutic plan concerning the uniqueness of the individual.
• The integrated treatment is considered the gold standard for patients with a dual diagnosis^(41,42).

The integrated treatment model pursues two objectives:

• First, to facilitate access to health care for patients with dual diagnosis and to optimize their individualized treatment.
• Secondly, to harmonize coherently the psychopharmacological intervention with that of the psychosocial model.

At the same time, a national vision is also needed to influence public health policies^(41,42).
 

Discussion

The dual diagnosis is a real clinical context that should be considered a rule rather than an exception. On the one hand, the coexisting of two mental disorders will result in a negative mutual influence of both conditions. On the other hand, dual diagnosis might be a significant cause of treatment resistance. This state of affairs should make the mental health worker more careful in assessing a person presenting for one of two conditions of dual diagnosis.

Functional neuroimaging research has repeatedly shown that the neural basis and neurotransmitter systems could overlap in the pathogenesis of both psychiatric conditions belonging to the dual diagnosis. This is the reason why, in psychiatric practice, a psychotropic class of medications can be helpful in both mental disorders. For example, an antidepressant might improve an addictive behavior without depressive symptoms being necessarily present in the clinical picture. Hence, tianeptine has been shown to decrease the craving in alcohol-dependent patients even after the depressive symptoms have been remitted.

Undoubtedly, psychosocial and pharmacological interventions should be individualized and optimized for each psychiatric patient with or without a dual diagnosis. It remains a debatable clinical issue whether conditions belonging to the dual diagnosis should be treated sequentially, depending on their severity, or simultaneously. However, in clinical practice, psychiatrists more often agree on the simultaneous treatment of both psychiatric conditions.

Last but not least, it should be taken into account that the presence of a dual diagnosis may lead to an increased risk of suicide through a cumulative effect of both constitutive psychiatric conditions. 

 

 

 

Autori pentru corespondenţă: Virgil-Radu Enătescu E-mail: renatescu@yahoo.com

CONFLICT OF INTEREST: none declared.

FINANCIAL SUPPORT: none declared.

This work is permanently accessible online free of charge and published under the CC-BY.